Stem Cells from Human Exfoliated Deciduous Teeth and their Promise as Preventive and Therapeutic Strategies for Neurological Diseases and Injuries

Stem cells from human exfoliated deciduous teeth (SHEDs) are relatively easy to isolate from exfoliated deciduous teeth, which are obtained via dental therapy as biological waste. SHEDs originate from the embryonic neural crest and therefore have considerable potential for neurogenic differentiation. Currently, an increasing amount of research attention is focused on the therapeutic applications of SHEDs in neurological diseases and injuries. In this article, we summarize the biological characteristics of SHEDs and the potential role of SHEDs and their derivatives, including conditioned medium from SHEDs and the exosomes they secrete, in the prevention and treatment of neurological diseases and injuries.

Application of collagen and mesenchymal stem cells in regenerative dentistry

: Collagen is an important macromolecule of extracellular matrix (ECM) in bones, teeth, and temporomandibular joints. Mesenchymal stem cells (MSCs) interact with the components of the ECM such as collagen, proteoglycans, glycosaminoglycans (GAGs), and several proteins on behalf of variable matrix elasticity and bioactive cues. Synthetic collagen-based biomaterials could be effective scaffolds for regenerative dentistry applications due to mimicking of host tissues’ ECM. These biomaterials are biocompatible, biodegradable, readily available, and non-toxic to cells whose capability promotes cellular response and wound healing in the craniofacial region. Collagen could incorporate other biomolecules to induce mineralization in calcified tissues such as bone and tooth. Moreover, the addition of these molecules or other polymers to collagen-based biomaterials could enhance mechanical properties, which is important in load-bearing areas such as the mandible. A literature review was performed via reliable internet database (mainly PubMed) based on MeSH keywords. This review first describes the properties of collagen as a key protein in the structure of hard tissues. Then, it introduces different types of collagens, the correlation between collagen and MSCs, and the methods used to modify collagen in regenerative dentistry including recent progression on the regeneration of periodontium, dentin-pulp complex, and temporomandibular joint by applying collagen. Besides, the prospects and challenges of collagen-based biomaterials in the craniofacial region pointes out.

Amniotic fluid stem cells: what they are and what they can become

: In the last two decades, fetal amniotic fluid stem cells progressively attracted attention in the context of both basic research and the development of innovative therapeutic concepts. They exhibit broadly multipotent plasticity with the ability to differentiate into cells of all three embryonic germ layers and low immunogenicity. They are convenient to maintain, highly proliferative, genomically stable, non-tumorigenic, perfectly amenable to genetic modifications, and do not raise ethical concerns. However, it is important to note that among the various fetal amniotic fluid cells, only c-Kit+ amniotic fluid stem cells represent a distinct entity showing the full spectrum of these features. Since amniotic fluid additionally contains numerous terminally differentiated cells and progenitor cells with more limited differentiation potentials, it is of highest relevance to always precisely describe the isolation procedure and characteristics of the used amniotic fluid-derived cell type. It is of obvious interest for scientists, clinicians, and patients alike to be able to rely on up-to-date and concisely separated pictures of the utilities as well as the limitations of terminally differentiated amniotic fluid cells, amniotic fluid-derived progenitor cells, and c-Kit+ amniotic fluid stem cells, to drive these distinct cellular models towards as many individual clinical applications as possible.

Therapeutic Effects of Physical Exercise and the Mesenchymal Stem Cell Secretome by Modulating Neuroinflammatory Response in Multiple Sclerosis

Multiple sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by central nervous system (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.

Advanced platelet-rich fibrin extract treatment promotes the proliferation and differentiation of Human Adipose-Derived Mesenchymal Stem Cells through activation of tryptophan metabolism

Background: Advanced platelet-rich fibrin extract (APRFE) contains a high concentration of various cytokines that are helpful for improving stem cells repair function. Objective: However, the underlying mechanism of APRFE improving stem cell repairing is not clear. Methods: We produced APRFE by centrifuging fresh peripheral blood samples and isolated and identified human adipose-derived mesenchymal stem cells (ADMSCs). The abundance of cytokines contained in APRFE was detected by the Enzyme-linked immunosorbent assay (ELISA). The ADMSCs treated with or without APRFE were collected for transcriptome sequencing. Results: Based on the sequencing data, the expression profiles were contracted. The differentially expressed genes and lncRNA (DEGs and DElncRNAs) were obtained using for the differential expression analysis. The lncRNA-miRNA-mRNA network was constructed based on the miRNet database. The further enrichment analysis results showed that the biological functions were mainly related to proliferation, differentiation, and cell-cell function. To explore the role of APRFE, the protein-protein interaction network was constructed among the cytokines included in APRFE and DEGs. Furthermore, we constructed the global regulatory network based on the RNAInter and TRRUST database. The pathways in the global regulatory network were considered as the core pathways. We found that the DEGs in the core pathways were associated with stemness scores. Conclusion: In summary, we predicted that APRFE activated three pathways (tryptophan metabolism, mTOR signaling pathway, and adipocytokine signaling) to promote the proliferation and differentiation of ADMSCs. The finding may be helpful for guiding the application of ADMSCs in the clinic.

Efficacy and Safety of Mesenchymal Stromal cells Therapy for COVID-19 Infection: A Systematic Review and Meta-analysis

Background: Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease prevalent worldwide with a high mortality rate, and there is currently no specific medicine to treat patients. Objective: We aimed to assess the safety and efficacy of stem cell therapy for COVID-19 by providing references for subsequent clinical treatments and trials. Method: We systematically searched PubMed, Embase, Cochrane, and Web of Science, using the following keywords: “stem cell” or “stromal cell” and “COVID-19.” Controlled clinical trials published in English until 24th August 2021 were included. We followed the PRISMA guidelines and used Cochrane Collaboration’s tool for assessing the risk of bias. We analysed the data using a fixed-effect model. Results: We identified 1779 studies, out of which eight were eligible and included in this study. Eight relevant studies consisted of 156 patients treated with stem cells and 144 controls (300 individuals in total). There were no SAEs associated with stem cell therapy in all six studies, and no significant differences in AEs (p = 0.09, I2 = 40%, OR = 0.53, 95% CI: 0.26 to 1.09) between the experimental group and control group were observed. Moreover, the meta-analysis found that stem cell therapy effectively reduced the high mortality rate of COVID-19 (14/156 vs. 43/144; p<0.0001, I2 =0%, OR=0.18, 95% CI: 0.08 to 0.41). Conclusion: This study suggests that MSCs therapy for COVID-19 has shown some promising results in safety and efficacy. It effectively reduces the high mortality rate of COVID-19 and does not increase the incidence of adverse events.

Application of Nanomaterials in Regulating the Fate of Adipose-derived Stem Cells

Adipose-derived stem cells are adult stem cells which are easy to obtain and multi-potent. Stem-cell therapy has become a promising new treatment for many diseases, and plays an increasingly important role in the field of tissue repair, regeneration and reconstruction. The physicochemical properties of the extracellular microenvironment contribute to the regulation of the fate of stem cells. Nanomaterials have stable particle size, large specific surface area and good biocompatibility, which has led them being recognized as having broad application prospects in the field of biomedicine. In this paper, we review recent developments of nanomaterials in adipose-derived stem cell research. Taken together, the current literature indicates that nanomaterials can regulate the proliferation and differentiation of adipose-derived stem cells. However, the properties and regulatory effects of nanomaterials can vary widely depending on their composition. This review aims to provide a comprehensive guide for future stem-cell research on the use of nanomaterials.